Mstn Ii - Lecture 22

Front 1

Von Gierke's Disease

Back 1

caused by G6P deficiency

characterized by hypoglycemia and a lack of glycogenolysis induced by epinephrine and glucagon

Front 2

Glycogen Storage Diseases

Back 2

Type Ia or von Gierke
Andersen's disease
McArdle's disease

Front 3

Anderson's disease

Back 3

defect in the glycogen branching enzyme

symptoms: liver cirrhosis, abnormal glycogen levels, and diminished hyperglycemic response to epinephrine

Front 4

McArdle's disease

Back 4

defect in muscle glycogen phosphorylase

characterized by reduction in blood lactate and pyruvate levels after exercise, no post-exercise drop in pH and a normal response to epinephrine.

Front 5

Glucose

Back 5

- cross blood brain barrier
- a lot of osmotic potential
- high potential for water to rush into the cell and lyse

Front 6

Triacylglycerols

Back 6

- extremely high-energy yield
- stored in convenient, compact form due to its hydrophobicity
- does not cross blood brain barrier b/c insoluble nature
- only used in aerobic conditions
- slow ATP generation

Front 7

Ketone Bodies

Back 7

- negatively charged
- readily soluble
- cross blood brain barrier
- only used aerobically
- slow ATP generation

Front 8

Amino Acid and Proteins

Back 8

- provide carbon skeleton for manufacturing glucose or ketone bodies
- last resort for filling the priority of maintaining blood glucose level

Front 9

Glycogen is a polymer of glucose linked by

Back 9

alpha 1-4 glycosidic

Front 10

Every x-y residues, glucose branches at ....

Back 10

every 8-10 residues, molecule branches at an alpha 1-6 linkage.

Front 11

General properties of Glycogen

Back 11

- soluble
- prohibitive osmotic force for cells
- plays different roles in the liver and in skeletal muscle
- stored in small granules in the cytoplasm

Front 12

Glycogen in Liver

Back 12

maintain glucose homeostasis

Front 13

Glycogen in Muscle cells

Back 13

provide a burst of energy in times of activity

Front 14

amylopectin

Back 14

- one of the two components of starch
- branches every 24-30 residues

Front 15

Non-reducing ends of glucose

Back 15

- where carbons 4 and 6 are located and are the 'business end' of the molecule.
- where glucose is added and where glycogen is broken down.

Front 16

Advantage for storing glucose in the form of glycogen

Back 16

- rapid mobilization under aerobic and anaerobic conditions

Front 17

Disadvantage to using glycogen

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- hygroscopic
- can bind about 3-4 times its weight in water, limiting the amount of glycogen that we can store
- nearly depleted after 12 hours of fasting

Front 18

glycogen phosphorylase

Back 18

- breaks down glycogen in glycogen mobilization
- phosphorylates glycogen at a non-reducing end and cleaves the alpha 1-4 linkage

Front 19

After glycogen phosphorylase, glucose unit is released as:

Back 19

- glucose 1 phosphate
- looks similar to G6P

Front 20

Phosphoglucomutase

Back 20

- moves the phosphate on G1P to make G6P
- allowing it to participate in the glycolytic pathway

Front 21

Limitation of glycogen phosphorylase

Back 21

cannot cleave glucose from glycogen once it gets closer than 4 residues to a branch point in the molecule.

Front 22

Debranching enzyme

Back 22

- second enzyme involved in mobilizing glucose
- hydrolysis of glycogen
- slow enzyme
- moves trisaccharide unit until alpha 1-4 linkages from the limiting area of the molecule to the non-reducing end of another branch of glycogen
- then utilizes its alpha 1-6 glucosidase activity to hydrolyze and release the remaining glucose unit.

Front 23

glucose 6 phosphatase

Back 23

- enzyme in the membrane of the ER catalyzes the hydrolysis of glucose to inorganic phosphate and glucose.

Front 24

GLUT-2 transporter

Back 24

glucose is free to exit the cell through the GLUT-2 transporter and enter the blood

Front 25

First step of Glycogen synthesis

Back 25

- formation of UDP-glucose

Front 26

UDP- glucose

Back 26

- first step of glycogen synthesis
- activated form of glucose

Front 27

G1P and UDP are covalently linked at:

Back 27

1' carbon

Front 28

UDP pryophosphorylase

Back 28

catalyze the formation of UDP-glucose

Front 29

glycogen synthase

Back 29

- catalyze the polymerization of glucose
- needs a pre-existing polymer to work off of

Front 30

glycogenin

Back 30

- in glycogen synthesis, the primer is provided by this protein
- catalyze the addition of 8 glucose units to a tyrosine residue on itself
- then allow glycogen synthase to take over.

Front 31

Glycogen synthase makes new linkages between...

Back 31

carbons 1 and 4 at the expense of the linkage between glucose and UDP.

Front 32

Branching enzyme

Back 32

- involved in glycogen synthesis
- makes alpha 1-6 linkages periodically to branch te polymer of glycogen.
- catalyzes the rxn by transferring a seven residue segment from the non-reducing end of glycogen to another location on the same or another chain.

Front 33

glycogen phosphorylase - phosphorylated

Back 33

major enzyme involved in breaking down glycogen

active when phosphorylated

phosphorylase a

Front 34

phosphorylated b

Back 34

inactive version

Front 35

phosphorylase kinase

Back 35

catalyze the phosphorylation of a serine residue on glycogen phosphorylase

also has two forms

Front 36

phosphorylase kinase a

Back 36

active form of phosphorylase kinase

phosphorylated

Front 37

phosphatases

Back 37

phosphate groups are removed by this class of molecules

Front 38

phosphoprotein phosphatase - 1

Back 38

phosphorylase kinase is deactivated by this molecule

Front 39

protein kinase A

Back 39

- cyclic AMP (cAMP) dependent kinase that is activated by cAMP levels increasing.

- one of the two major proteins that can phosphorylate glycogen synthase (turning it off)

Front 40

phosphorylated glycogen synthase

Back 40

inactive

Front 41

glycogen synthase kinase 3

GSK-3glu

Back 41

second important protein that can phosphorylate glycogen synthase (turning it off)

Front 42

Insulin and GSK-3

Back 42

insulin inhibit GSK-3's ability to phosphorylate glycogen synthase.

protects glycogen synthase from the deactivating effects of phosphorylation, and allows the body to make glycogen.

Front 43

Red Blood Cell

Back 43

- no nuclei or mitochondria
- completely dependent on glucose for energy
- only metabolize fuel anaerobically

Front 44

Brain

Back 44

major glucose demand b/c it utilizes glucose almost exclusively, oxidizing it all the way to CO2 and H2O.

under starving conditions, brain cell use ketone bodies as fuel, meet about 1/3 of the energy demands.

Front 45

skeletal muscles

Back 45

under resting conditions, fatty acids are used for fuel rather than glucose.

exercise: glycogen is mobilized to make glucose for the glycolytic pathway. b/c muscles need energy much more quickly.

Front 46

adipose tissue

Back 46

stores fatty acids in the form of triacylglycerol

availability of glucose plays a critical role in determining if triacylglycerol is stored in these cells.

Front 47

liver

Back 47

fatty acids come from there

plays a crucial role in glucose homeostasis and pathways like glycolysis do not play the same role in the liver as they do in other organs

Front 48

liver, after meal

Back 48

glycolysis has the major role of forming acetyl-coA to make fatty acids

Front 49

liver, fasting

Back 49

glucose is very low, which stimulates gluconeogensis: the reverse of glycolysis which converts pyruvate to glucose and releases it into the blood.

Exclusively in the liver, and a small amount in the kidneys.

Front 50

glucokinase

Back 50

liver does not have hexokinase 1, it has this

much lower activity than hexokinase.

to protect newly formed glucose that is destined to be exported from the liver cell.